This grant proposal is a continuation of our previous work dealing with the psychopharmacology of the lithium ion. The scope has been considerably expanded; we now plan on concentrating our research efforts in using lithium as a tool to explore the biochemical framework underlying the affective disease entities. In this regard, a number of studies are proposed exploring the metabolism of biogenic amines: determination of cerebrospinal fluid D beta H activity; examination of MHPG, HVA, and 5-HIAA in CSF; turnover rates and relative specific activities of NE3H2 as well as of its major metabolites and biogenic amine transport in platelets; and red blood cell (RBC) COMT and the RBC/plasma lithium relationship to distinguish different clinical pictures. The effect of lithium on a variety of endocrines and the effectsof this ion on the hypothalamus-pituitary axis will continue to be explored; this includes thyroid and adrenocortical studies as well as further examination of carbohydrate metabolism. Clinical studies will concentrate on exploring lithium's potential therapeutic effects in other related disorders, such as cyclic mood disturbances related to the menstrual cycle (premenstrual tension). Continuing to define a role for lithium in acute depressive recurrences is considered to be of central importance in considering lithium as an agent capable of affecting a disease entity rather than merely the symptoms of the related illnesses (e.g., manic-depressive disorder).